Naphthoquinone oxides and method of preparing the same



Patented Mar. 2, 1943 UNITED STATES PTENT OFFICE NAPHTHOQUINONE OXIDES AND METHOD OF PREPARING THE SAME Louis F. Fieser, Belmont, Mass, assignor to Research Corporation, New York, N. Y., a crporation of New York No Drawing. Application July 23, 1940, Serial No. 347,042

9 Claims. (Cl. 260-348) This invention relates to 1,4-naphthoquinone- IR 2 I and each R, stands for hydrogen or an alkyl or a fi-alkenyl group, at least one R being an alkyl or a fi-alkenyl group, and each R1 stands for hydrogen or an alkyl group.

In this disclosure an alkyl group is understood to be a saturated monovalent hydrocarbon group and a e-alkenyl group is understood to be a monovalent unsaturated hydrocarbon group.

The preparation of the oxide of 1,4-naphthoquinone by treating it with aqueous hypochlorites has been reported. (Zincke, Ben, 25, 3602 (1892). Attempts to apply this process to alkyl and. alkenyl substituted 1,4-naphthoquinones have resulted in failure. does not proceed to completion or secondary reactions are involved so that a complex mixture of material is obtained which is extremely difficult to purify. In addition, the process is inconvenient'in its application due to the fact that extremely large volumes of liquid must be handled.

Weitz, SchObbert and Seibert, Ben, 68, 1165 (1935) prepared the oxide of 1,4-naphthoquinone by treating this quinone in methanol with 30% H202 and 2N NaOH (20 cc. per 3.2 g. of quinone). The reaction was slow, allowing opportunity for destruction of the sensitive quinone by the alkali, no yield was recorded (and presumably therefore was low), and no evidence was presented to show The reaction either that the reaction is applicable to any other examples in the a-naphthoquinone series. This proc' 'ess surely could not be applicable to the prepara tion of the oxides of the 2- or 3-5-alkenyl substituted a-naphthoquinones, which are highly sensitive to and rapidly destroyed by strong alkalies of the type of NaOH or KOH.

Even with 2 or 3 alkyl substituted quinones, the method, if applicable, doubtless would give but poor yields, for the sensitivity of-the resulting oxides to alkali has been fully established.

I have discovered that napththoquinone and its alkyl and/or fl-alkenyl derivatives react with peroxides such as hydrogen peroxide in the presence of carbonates of the group including sodium, potassium, lithium and ammonium carbonates to give high yields of the corresponding pure naphthoquinone oxides. The reaction proceeds very rapidly and the process is easy to use and produces products which are easily purified. In general, the method consists in adding aqueous sodium carbonate and hydrogen peroxide solutions to a solution or suspension of the naphthoquinone in a suitable solvent of the group including methyl and ethyl alcohol and dioxan. 2,3.- oxides of the 1,4-naphthoquinone are formed: The oxides possess anti-hemorrhagic activity and are useful for the preparation of othernaphthoquinone derivatives as is shown bythe fact that certain of the oxides react with strong alkali or acid to form hydroxy-naphthoquinones.

In the examples given below, preferred procedures in accordance with the invention are given but it is to be understood that modifications may be made without departing from the spirit and scope of the invention and that these examples are given by way of illustration and not of limitation.

A general procedure in accordance with the invention is as follows. One part by weight in grams of the selected 1,4-naphthoquinone, is dissolved in ethyl alcohol and treated. at -75" C. with one to three parts by volume in cubic centimeters of 30% hydrogen peroxide followed by a solution of 1/ 10 to 1 part by weight in grams of sodium carbonate in 2 parts by volume in cubic anti/hemorrhagic activity when administered at a dosage of 100-200 micrograms.

I claim:

1. Compounds of the formula I R R1 1 R1 0 in which one R is a p-alkenyl group, the other R Analysis Naphthoquinone M. P. of oxide Cryst. form. of oxide Carbon Hydrogen Found Calc. Found Calc.

2-methyl-1,4-naphthoquinone 95. 5-96. 5 Long needles.-. 70. 38 70. 4. 36 4. 26 2,S-dimethyl-l,4-naphthoquin0ne 104. 0-104. 5 ..do 71. 26 71. 27 5. 09 4. 99 2,6-dimethyl-L4-naphthoquinone 97-98 Prisms ,71. 23 71. 27 5. 07 4. 99 2,7-dimethyl-l,4-naphthoquinone 9192 Slender needles. 71. 29 71. 27 5. 09 4. 99

Emample 1 Preparation of 2-farnesyland 2-geranyl-1,4-

naphthoquinone-2,3-oxides To a solution of 0.37 gram of 2-farnesyl-1,4- naphthoquinone in 10 cc. of dioxan' is added a solution of 0.2 gram of sodium carbonate and .1 cc. of hydrogen peroxide in 3 cc. of water. The mixture is allowed to stand for 24 hours at room temperature and then 10 cc. of ethyl alco- H01 and 1 cc. of hydrogen peroxide added. Then, after several days, the nearly colorless mixture is diluted with water and extracted with ethyl ether. The extract is washed thoroughly with water, clarified with Norite, dried and evapgram of a faintly yellowish tained as a faintly yellowish oil. 55

I Erample 2 I 7, 'Preparation of -2-phytyl-1,4-naphthoduinon as oxide it 0.5 gram 'of 2-phytyl-1,4-naphthoquinone,0.5 60

'cc. of 30% hydrogen peroxide and 0.5 gram of anhydrous sodium carbonate dissolved in 1 cc. ofwater are processed according to the method outlined in Example 2. "About 0.47 gram of a :61

straw-colored liquid is obtained.

Analysis: calculated for C30H4402-Carb0n 79.58, hydrogen 9.81; foundcarbon 79.90, hydrogen 9.76.

.The product, when heated with alcoholic a1- kali, gives a temporary green color which changes to a reddish brown. 111 chicks, it shows 'naphthoquinone is a member of the 25 is a member of the group consisting of hydrogen and monovalent aliphatic hydrocarbon groups 1 and each R1 is a member of the group consisting of hydrogen and alkyl.

2. Compounds as defined in claim 1 in which one R is a fl-alkenyl group and the other R is an alkyl group. 1 :7' 3. 2-farnesyl-l,4-naphthoquinone-2,3-oxide. 4. Process for the production of 1,4-naphthoquinoneoxides which comprises reacting a "1,4 naphthoquinone with a peroxide in the presence of an alkali carbonate and a neutralorganlc solvent. a

5. Process as defined in claim 4 in which the peroxide is hydrogen peroxide.

6. Process as defined in claim 4 in which the alkali carbonate is sodium carbonate.

7. Process as defined in claim 4 in which the neutral organic solvent is a member of the group consisting of ethyl alcohol, methyl alcohol and dioxan.

8. Process as defined in claim 4 in which the peroxide is hydrogen peroxide, the alkali carbonate is sodium carbonate and the neutral organic solvent is a member of the group consist,- ing of methyl alcohol, ethyl alcohol and dioxan.

9. Process as defined in claim 4 in which the resented by the formula in which at leastv one R. stands for a monovalent aliphatic hydrocarbon group, the other B. being a member of the group consisting of hydrogen and monovalent aliphatic hydrocarbon groups.

and each R1 stands for a member of the group consisting of hydrogen and alkyl.

Louis 

